[unreadable] The effects of ooplasmic factors on genome function and development remain poorly understood, despite an extensive body of literature indicating the existence of such effects. Understanding these effects is essential for a thorough understanding of the developmental mechanisms that initiate each new life, and that direct normal growth and development. Moreover, understanding these effects has significant clinical relevance in the area of assisted reproduction technology (ART), as the treatment of human infertility continues to advance through the implementation of novel microsurgical procedures being implemented in the absence of any controlled scientific data addressing their safety or efficacy. Abundant data from mouse studies reveal the potential for epigenetic effects of 'foreign' cytoplasm on the embryonic genome, leading to effects on embryo viability or developmental abnormalities, some of which are transmitted to the next generation. This proposal addresses the biology of epigenetic programming during oocyte development and maturation, the epigenetic effects of ooplasm on the embryonic genome, the potential for aberrant epigenetic modifications arising as a result of ARTs methods for application at other stages. We will exploit a model system that is based on the existence of genetically diverse egg modifiers, which differentially modify, epigenetically, the maternal and paternal genomes. The proposed studies will provide new basic data about ooplasm-nuclear interactions as well as data relevant to the clinical application of microsurgical procedures. [unreadable] [unreadable]